HiHat

Treatment tested

• Cladribine

  DNA inhibitor

• Rituximab

  B-lymphocyte antigen CD20 binding agent

Other measures (13)

Inclusion Criteria: * Diagnosis of RRMS according to the 2017 revised McDonald criteria, * With disease activity within the preceding year in the form of: a clinical relapse, and/or evidence of ≥2 T2 lesions on MRI scan, and or presence of gadolinium enhancing lesions on an MRI scan, * Age 18 - 50 years (inclusive) of age, * Disease duration ≤10 years (since MS diagnosis), * EDSS 0 - 5.5 (inclusive), * Signed informed consent. Exclusion Criteria: * Diagnosis of progressive MS, * Previous use of rituximab (or any other B-cell depleting monoclonal antibody) and/or cladribine, * Pregnant or lactating women, * Unwilling to use contraception during the treatment period and the first year after completing the treatment course, * Patients having contraindication for or otherwise not compliant with MRI investigations, * Simultaneous treatment with other immunosuppressive drugs, * Infection with human immunodeficiency virus (HIV), * Active, severe infections (e.g. hepatitis or tuberculosis), * Severe cardiac disorder, * Moderate or severe renal impairment (eGFR \<60). * Active malignancy, * No prior exposure to varicella virus, * Vaccination within 4 weeks of first dose of study medication, * Severe psychiatric condition.

The HiHat trial is a Phase 2 study aimed at evaluating the safety and feasibility of sequential treatment with rituximab and cladribine in patients with relapsing-remitting multiple sclerosis (RRMS). The study follows a prospective, open-label, single-arm design, with 60 RRMS patients receiving both treatments in a controlled regimen: two cycles of rituximab (1,000 mg each, biweekly) followed by two cycles of cladribine (30 mg per cycle for three days per cycle) spaced one month apart. Participants are monitored over 24 months through clinical assessments, MRI, and biomarker analyses. The primary objective is to evaluate whether the rate of serious adverse events (SAE) is acceptably low. Secondary objectives include assessing impacts on MRI lesion count, relapse rates, disability progression, quality of life, and safety.